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A monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) significantly reduced the risk of COVID-19–related hospitalizations and death from any cause in the phase 3 portion of an adaptive trial of outpatients.
Researchers, led by David Weinreich, MD, MBA, executive vice president of the drug cocktail’s manufacturer Regeneron, found in the randomized trial that the combination also resolved symptoms and reduced the SARS-CoV-2 viral load more quickly compared with placebo.
Findings were published online Wednesday in the New England Journal of Medicine.
COVID-related hospitalization or death from any cause occurred in 18 of 1355patients (1.3%) in the group getting 2400 mg infusions of the study drug compared with 62 (4.6%) of 1341 in the matching placebo group, indicating a relative risk reduction of 71.3%; P < .001.
Sunil Joshi, MD, president of the Duval County Medical Society Foundation and an immunologist in Jacksonville, Florida, told Medscape Medical News that these findings confirm benefits of REGEN-COV and are very good news for a patient group that includes those age 65 and older with high blood pressure, diabetes or obesity; and for people not vaccinated, who are all at high risk of hospitalization or death if they get COVID-19.
“Vaccines are critically important,” he said, “but if you were to be infected and know that there’s a way to keep yourself out of the hospital, this is very good news.”
Researchers Seek Lowest Doses
This trial found that the effect was similar when researchers cut the doses in half. These outcomes occurred in 7 of 736 (1%) of patients given 1200 mg of REGEN-COV and in 24 (3.2%) of 748 in the matching placebo group (relative risk reduction, 70.4%; P = .002).
Symptoms were resolved on average 4 days earlier with each REGEN-COV dose than with placebo (10 days vs 14 days; P < .001 for both comparisons).
Weinreich told Medscape Medical News trials will continue to find the lowest effective doses that can stand up to all evolving variants.
“This is one of those settings where you don’t want to underdose. You’ve got one shot at this,” he said. “We’d love to do lower doses. It would be more convenient and we could treat more patients, but if it generates more clinical failures or doesn’t work with certain variants, then you’ve done a huge disservice to the world.”
Also new in this study is that researchers tested not only seronegative patients, but patients at high risk regardless of blood antibody status, he said.
“It’s the first suggestion of data that if you’re breaking through a vaccine and you’re at high risk, the use of the cocktail is something to strongly consider because treatment early is better than treatment later,” Weinreich said.
In addition to efficacy, the phase 3 trial demonstrated the cocktail had a good safety profile. Serious adverse events occurred more often in the placebo group (4%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%). Infusion reactions (grade 2 or higher) occurred in less than 0.3% of patients in all groups.
William Fales, MD, state medical director for the Michigan Department of Health and Human Services, said the results confirm the promise of REGEN-COV for reducing hospitalizations and death in a peer-reviewed publication.
COVID-19 a Moving Target
However, Fales noted that COVID-19 is a moving target with emerging variants. The criteria for populations at high risk have also broadened since the start of the study, he said.
“A great example is pregnancy is now included as high risk, and that would have likely been a specific contraindication of patients in this clinical trial,” he said.
Fales said Michigan has been using both REGEN-COV and the Eli Lilly combination of bamlanivimab and etesevimab, which also has an emergency use authorization (EUA) from the US Food and Drug Administration (FDA), with positive results.
REGEN-COV has an EUA to treat people who are at high risk of serious consequences from COVID-19, including those who are already infected (nonhospitalized) or those in certain post-exposure prophylaxis settings.
“We’re seeing very low hospitalization rates and few deaths in a state that is predominately Delta,” Fales said. “So, this makes us feel that we’re doing the right thing and supports the current efforts around the country to make monoclonal antibody therapy available to high-risk patients.”
Joshi noted that trial results have been emerging from other monoclonal antibody cocktails with different COVID-19 patient groups.
However, he told Medscape Medical News, “How much more effective they would be than this is something we’d have to look at, as 71% effectiveness in keeping people out of the hospital is pretty good for any treatment.”
“These are great numbers, but vaccination itself keeps you from getting the disease in the first place and not just for a short time period. This treatment is just that — a treatment. It gets you through that episode but it doesn’t mean you won’t get sick again. You don’t develop an immune response as you do with the vaccine,” he said.
Weinreich agreed: “This is not a substitute for a vaccine except for the small group who get the vaccine and their bodies can’t respond to it because they’re significantly immunocompromised.”
The results from this paper “are one piece of a large, multistudy phase 3 program that basically spans from prophylaxis all the way to hospitalization and pretty much the gamut — all of them — have worked. All of these studies have shown dramatic improvement in whatever the definitive regulatory endpoint is,” Weinreich said.
He said discussions are ongoing for full regulatory approval in the United States and for expanding the EUA for other populations, including preexposure prophylaxis, “which the [United Kingdom’s] authority has already granted us but the FDA has not.”
The study is funded by Regeneron and the US Department of Health and Human Services.
Disclosure forms provided by the authors are available with the full text of this article. Weinreich is a vice president of Regeneron. Joshi reports no relevant financial relationships. Fales holds stock in Eli Lilly.
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and Nurse.com, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick